Superoxide anion increases intracellular free calcium in human myometrial cells

We investigated the effects of superoxide anion on the intracellular free calcium concentration (Ca2+]i) in human cultured myometrial cells using a calcium-sensitive fluorescent dye, indo-1, and a digital imaging fluorescence microscopic system. Hypoxanthine (HX) plus xanthine oxidase induced a rise in Ca2+]i in a manner dose-dependent on xanthine oxidase. The increase in Ca2+]i in the absence of extracellular calcium (Ca2+]ex) was 10% of that in the presence of Ca2+]ex. Nifedipine, which blocks voltage-sensitive calcium channels, also reduced the increase in Ca2+]i induced by HX-xanthine oxidase. Superoxide dismutase or superoxide dismutase plus catalase, which metabolizes superoxide anion, inhibited the effect of HX-xanthine oxidase on Ca2+]i. The desensitization of the effect of superoxide anion on Ca2+]i was investigated by pulsatile administration of HX and xanthine oxidase. Desensitization was observed on pulsatile administration of HX-xanthine oxidase at 2-min intervals. These data suggest that superoxide production may participate in uterine contraction via Ca2+]i increase.